Project Summary/Abstract The role of environmental chemicals known as obesogens in the etiology of human adiposity has been increasingly appreciated. In this proposal, we aim to evaluate polycyclic aromatic hydrocarbons (PAHs) and heterocyclic aromatic amines (HAAs) in relation to weight change in human subjects. The carcinogenic effects of these ubiquitous pollutants are well-documented, and emerging evidence suggests that these chemicals may also disrupt endocrine functions through exerting estrogenic effects and other pathways. Limited human evidence, often from cross-sectional studies, also supports the hypothesis that these chemicals are potential obesogens, although prospective data are needed to substantiate the associations between these chemicals and excess weight gain in humans. We propose to 1) examine excretion of PAHs and HAAs in 24-hour urine samples in relation to short-term weight loss induced by energy restriction in the POUNDS Lost trial; 2) evaluate whether changes in urinary excretion of these chemicals during weight loss period predict weight regain in the POUNDS Lost trial; and 3) investigate associations between levels of these chemicals in 24-hour urine samples and long-term weight change in women and men participating in the Nurses' Health Study II (NHSII) and Coronary Artery Risk Development in Young Adults (CARDIA). In addition, in light of the pathways through which these two groups of chemicals may synergistically amplify each other's detrimental effects, we will also examine potential interactions between PAHs and HAAs on weight loss, weight regain, and long-term weight change in the studies. To ensure high quality scientific data, we have carefully designed our proposed studies. In the POUNDS Lost, NHSII, and CARDIA studies, we will quantify PAHs and HAAs in 24-hour urine samples to substantially improve the reproducibility of urinary measurements over time. In all three studies, body weight and a multitude of other variables that are related with body weight change have been collected repeatedly during follow-up, allowing for comprehensive, longitudinal data analyses. We will restrict the research to largely healthy, non-smoking individuals to minimize the impact of chronic diseases and smoking on the associations of interest. To accomplish the aims, we have assembled an experienced research team with interdisciplinary expertise in the fields of environmental health, obesity epidemiology, biomarker research, biostatistics and bioinformatics, and toxicology. We will collaborate with highly reputable labs at the Centers for Disease Control and Prevention to measure PAH and HAA levels in 24-hour urine samples. Data to be generated from this project will substantially deepen our understanding of the potential, obesogenic effects of PAHs and HAAs in human populations. Moreover, evidence from this proposed research will also aid in the development of policies or recommendations toward reducing exposures to these chemicals and improving human health.